This invention relates to solid state sensors. More particularly the invention is concerned with stabilized solid state sensors for the determination of concentrations of gases, especially pO.sub.2 and pCO.sub.2, and also, with an appropriate indicator, for the determination of pH, in liquid media, such as human blood.
The measurement in blood of pO.sub.2, pCO.sub.2, and pH is important during surgical procedures, post-operatively, and during hospitalization under intensive care, numerous sensor devices for the measurement and monitoring of such parameters are disclosed in the art. A sensor device, hereinafter referred to as a sensor, for determining the concentration of an analyte in a liquid medium, typically comprises an indicator having a characteristic which changes in the presence of the analyte in association with a suitable carrier or substrate which also acts as a transmission line for conveying a signal representative of said change to a suitable detector. For example, the use of pyrenebutyric acid as a fluorescent indicator for the determination of the concentration of oxygen in blood is known and the use of this sensor in conjunction with an optical fiber, wherein the fluorescent indicator is enclosed within a selectively permeable membrane, is disclosed in U.S. Pat. No. 4,476,870.
A sensor utilizing a fluorescent indicator and adapted to function satisfactorily in a biological environment should possess at least four characteristics: sensitivity, short response time, stability and bio-inertness.
Sensitivity depends upon the quantum efficiency of the fluorescent indicator, the concentration of the indicator present in the sensor and availability of the indicator to the substance, i.e. ion or gas, it must sense. Thus a sufficient amount of indicator must be available to produce a meaningful fluorescent response. However, if indicator molecules are too close together there occurs a type of behavior which is frequently detrimental to the sensor performance; this behavior is known as eximer fluorescence. Therefore, for a given indication there is an optimum indicator concentration for maximum sensitivity.
A further problem which must be solved in the construction of a fluorescent sensor is the availability of the indicator to the environment to be sensed. If the subject ions or gas cannot reach the indicator molecules the indicator will not respond to the presence or absence of said ions or gas. This problem is clearly related to the permeability of the structure in which the indicator molecules are embedded.
Also related to permeability is the response time. If the substance to be sensed (i.e. ions or gas) diffuses very slowly through the structure the response time of the sensor will be comparatively long which greatly reduces its usefulness.
A sensor for blood gas or blood pH should be capable of use over a period of many hours or days. Recalibration of a sensor which is used in vivo is clumsy and inefficient or even impossible. Thus, the stability of the sensor is a key factor in determining its utility. A common problem in existing fluorescent sensor design is the gradual loss of the indicator from the sensor. This not only reduces the sensitivity, thereby creating instability in the sensor's indication even at constant concentration of the substance being sensed but also releases a chemical indicator into the blood stream. A device which releases chemical substances into the blood stream can not be considered to be bio-inert. As used herein, the term "bio-inert" is defined to mean that characteristic of a device, i.e. a sensor, whereby any and all chemical substances which are part of the device are so securely bonded to the structure of the device that they are not released or leached away from the device under normal operating conditions.
In the prior art the problem of leaching of the indicating substance from the sensor, which is inherent when small molecules are embedded in a polymer matrix, was generally addressed by enveloping or embedding the indicator in a selectively permeable membrane.
In practice, the problem manifests itself as a progressive loss of sensitivity of the sensor as the indicator is lost; this requires a continual re-calibration of the sensor.
The stated prior art arrangement does not completely solve the problem, since a portion of the indicating substance is still leached from the sensor. Thus, the problem of re-calibration still remains, and, moreover, the released indicator goes into the patients bloodstream.
Accordingly, it is desirable to provide a sensor which is more stable in the sense that the indicator is not leached or washed away therefrom upon contact with body fluids.
The desired stability may be achieved, according to U.S. Pat. No. 5,019,350 by providing a sensor for the determination of the concentration of a dissolved substance in an aqueous medium comprising an optical fiber having a distal end to which is stably bonded an adherent, water-insoluble organic polymer having a plurality of fluorescent organic substituents, which may be the same or different, covalently bonded to said polymer through ester or amide linkages.
The combination of polymer and fluorescent organic substituents forms a fluorescent polymeric indicator, examples of which are indicators for pO.sub.2, pH and pCO.sub.2.
U.S. Pat. No. 5,262,037 discloses an electrochemical sensor for the determination of the partial pressure of oxygen in a bloodstream. This electrochemical sensor for pO.sub.2 may be used in combination with a pH sensor and a pCO.sub.2 sensor to form a multi-parameter sensor. In such a multi-parameter sensor the pH sensor and pCO.sub.2 sensor preferably are made in accordance with the disclosure in U.S. Pat. No. 4,889,407 which provides an optical waveguide sensor for determining an analyte in a medium, which sensor comprises an optical waveguide having a portion to be brought into contact with the medium, said portion having a plurality of cells arranged in an array which substantially covers the cross-sectional area of the waveguide, each of said cells containing an indicator sensitive to said analyte. The preferred waveguide is an optical fiber and indicators disclosed include absorption indicators for pH, such as phenol red and fluorescent indicators, such as .beta.-umbelliferone for pH or pCO.sub.2, and pyrene butyric acid for pO.sub.2. In preparing the sensor the indicator is deposited in the cells of the optical fiber in the form of a gel or solid by immersing the portion of the fiber containing the cells in a solution of the indicator and appropriate gel-forming ingredients, subjecting the immersed fibers to a vacuum so that the cells are evacuated to allow ingress of the solution and curing the gel so that the indicator is retained in the cells in a stable manner.
PCT Application Publication No. WO 91/05252 discloses a carbon dioxide monitor which comprises a substrate having thereon an indicating member comprising an intimate mixture of a transparent polymer vehicle, and an indicator material which undergoes a color change on exposure to carbon dioxide. The indicator material comprises a salt of an indicator anion and a lipophilic organic quaternary cation.
U.S. Pat. No. 5,005,572 discloses a detector for the determination of carbon dioxide in respiratory gases and a method for determining the proper placement of an intubation device in a patient's trachea. The carbon dioxide detector comprises a pH-sensitive dye, a solid phase support and a phase transport enhancer for enhancing a reaction between H.sub.2 CO.sub.3 and the pH-sensitive dye.
U.S. Pat. NO. 4,728,499 discloses a combination rapid response device for the detection of carbon dioxide in a gas mixture comprising an enclosure with a transparent window having mounted therein an indicator component comprising a carder to which is fixedly attached an indicating element including a chromogenic pH-sensitive indicator which changes color when the concentration of carbon dioxide in the surrounding atmosphere exceeds 2%. The device is used to determine the correct placement of an endotracheal catheter.
It has now been found that the stability and performance of sensors for the determination of an analyte in a medium, particularly for the determination of pO.sub.2, pCO.sub.2 and pH in both liquid and gaseous media, is greatly enhanced when an appropriate indicator is used in association with a polymeric silicone carbinol as described hereinafter.